Project Summary The long-term goal of this project is to understand the relationship between obesity and volumetric breast density, and use this knowledge to better identify women at high risk of breast cancer and optimize resource allocation for intervention. Breast density is widely accepted as one of the strongest risk factors for breast cancer, and new automated measurements of breast density have facilitated the increasing use of breast density in the clinical setting for risk prediction and risk-based screening. It is plausible that other breast cancer risk factors modify the effect of breast density on breast cancer, and assessing this question using new fully- automated measures of breast density is important as these measures have the potential to be fully-integrated into clinical settings. Obesity is one of the most common risk factors for breast cancer among women in the United States, and there are likely to be a large number of overweight and obese women with high breast density. It is biologically plausible that the joint effect of obesity and breast density on the breast microenvironment may put women with both conditions at increased risk of breast cancer. The objective of this proposal is to characterize the effect of BMI on volumetric measures of breast density among premenopausal and postmenopausal women (Aim 1), and evaluate if body mass index (BMI) modifies the effect of volumetric breast density on breast cancer risk such that obese women with high breast density are at highest risk (Aim 2). These aims will provide a critical understanding of the complex relationship between obesity, breast density and breast cancer risk among premenopausal and postmenopausal women. The assessment of interaction on both additive and multiplicative scales will ensure that our results have high relevance to understanding potential mechanisms of interaction and identifying subgroups of women that may benefit the most from intervention to reduce breast density or BMI, two readily modifiable risk factors. The interdisciplinary training environment for this proposal will provide the applicant the opportunity to gain technical skills, build research competency and develop content area expertise to further her career as a future independent researcher.